Throughout this application, various publications are referenced by author and date. Full citations for these publications may be found listed alphabetically at the end of the specification immediately the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein.
Ineffective healing of wounds is a serious problem in diabetes, contributing to increased morbidity (Reynolds, 1985; Galloway and Shuman, 1963; and Pearl and Kanat, 1988). The reparative response in wound healing is orchestrated by multiple cellular elements which work together in many ways, including infiltration of the lesion by inflammatory effector cells. Subsequent to this, fibroblastic elements together with inflammatory effector cells provide antibacterial mechanisms and promote removal of necrotic tissue, as well as laying down of new connective tissue. A fundamental disorder of glucose metabolism might perturb these complex and interactive protective processes. Previous work has suggested that cellular dysfunction in diabetic wound healing involves defective neutrophil function (Bagdade et al., 1978; Nolan et al., 1978; and Mowat and Baum, 1971), delayed infiltration of the wound with inflammatory cells (Greenhalgh et al., 1990 and Fahey et al., 1991), decreased production of collagen (Goodson and Hunt, 1977 and Goodson and Hunt, 1986), and diminished activity of endogenous growth factors, such as basic fibroblast growth factor (Giardino et al., 1994), which could provide a basis for the slower formation of granulation tissue and wound closure.